This invention relates to a process for the resolution of (.+-.)-pyrano-[3,4-b]indole-1-acetic acids to obtain the separate corresponding (+) and (-) optical enantiomers.
The racemic (.+-.)-pyrano[3,4-b]indole-1-acetic acids are well known anti-inflammatory and analgesic agents described by C. A. Demerson et al., U.S. Pat. No. 3,939,178, issued Feb. 17, 1976; C. A. Demerson et al., J. Med. Chem., 18, 189 (1975) and 19, 391 (1976).
The process of this invention involves the condensation of a racemic (.+-.)-pyrano[3,4-b]indole-1-acetic acid with (-)-borneol to obtain a separable diasteroisomeric mixture of the corresponding esters and hydrolyzing the (+) and (-) diastereoisomeric esters. A limited number of esterifications of a racemic acid with an optically active alcohol to give diastereoisomeric esters are described, for example, P. H. Boyle, Quarterly Reviews, 25, 323 (1971). In addition, a few total syntheses of optically active acids using optically active alcohols are described, for example E. Wehinger et al., Abstr. Papers Am. Chem. Soc. 182 Meet. MEDI 64/1981; B. Laangstroem et al., Chem. Abstr. 91, 193607 p (1979) for Chem. Scr., 13, 49 (1979); and P. E. Krieger et al., J. Org. Chem., 43, 4447 (1978).
The above described uses of optically active alcohols are for specific syntheses of various acids in limited quantities. Such use of optically active alcohols are known to be of little importance for the general resolution of racemic acids, see P. H. Boyle, cited above, at p.325. Usually the mixture of diastereoisomeric esters cannot be separated to obtain the individual enantiomers.
The process of this invention resulted from the discovery that a diastereoisomeric mixture of pyrano[3,4-b]indole-1-acetic acid (-)-borneol esters can be easily separated. This process gives individual (+) and (-)-enantiomers of a pyrano[3,4-b]indole-1-acetic acid in a commerically feasible operation and in high yield.